Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI61AF34I)
  Drug Name Methotrimeprazine Drug Info Isosorbide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Cns Agents Antianginal Agents
  Structure

 Mechanism of Methotrimeprazine-Isosorbide Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Methotrimeprazine Isosorbide
      Mechanism Hypotensive effects
Alpha-1 adrenergic receptor  Antagonist 		Hypotensive effects
Guanylate cyclase  Agonist
      Key Mechanism Factor 1
Factor Name Adrenergic receptor alpha-1 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Guanylate cyclase soluble Structure Sequence
Protein Family Adenylyl cyclase class-4/guanylyl cyclase family
Protein Function
There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. Activated by nitric oxide in the presence of magnesium or manganese ions.
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Methotrimeprazine and Isosorbide 

Recommended Action
      Management Close clinical monitoring for development of hypotension is recommended if phenothiazines or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the elderly. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery.

References
1 Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
2 Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274. [PMID: 2857531]
3 Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9. [PMID: 7663034]
4 Product Information. Abilify (aripiprazole). Bristol-Myers Squibb, Princeton, NJ.
5 Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
6 Product Information. Geodon (ziprasidone). Pfizer US Pharmaceuticals, New York, NY.
7 Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
8 Product Information. Risperdal (risperidone). Janssen Pharmaceutica, Titusville, NJ.
9 Product Information. Seroquel (quetiapine). Zeneca Pharmaceuticals, Wilmington, DE.
10 Product Information. Zyprexa (olanzapine). Lilly, Eli and Company, Indianapolis, IN.
11 White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4. [PMID: 3530167]